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Title: Variants at the promoter of the interleukin-6 gene are associated with severity and outcome of pneumococcal community-acquired pneumonia
Authors: Martín-Loeches, Ignacio
Solé-Violán, Jordi
Rodríguez De Castro, Felipe 
García-Laorden, M. Isabel
Borderías, Luis
Blanquer, José
Rajas, Olga
Briones, M. Luisa
Aspa, Javier
Herrera-Ramos, Estefanía
Marcos-Ramos, José Alberto
Sologuren, Ithaisa
González-Quevedo, Nereida
Ferrer-Agüero, José María
Noda, Judith
Rodríguez-Gallego, Carlos 
UNESCO Clasification: 32 Ciencias médicas
320508 Enfermedades pulmonares
320102 Genética clínica
Keywords: C-Reactive Protein
Coronary Revascularization
Inflammatory Response
Sepsis, et al
Issue Date: 2012
Journal: Intensive Care Medicine 
Abstract: Conflicting results about the role of genetic variability at IL6, particularly the -174 G/C single nucleotide polymorphism (SNP), in sepsis have been reported. We studied the genetic variability at IL6 in patients with community-acquired pneumonia (CAP) and pneumococcal CAP (P-CAP).This was a multicenter, prospective observational study. IL6 -174 was analyzed in 1,227 white Spanish patients with CAP (306 with P-CAP). IL6 1753 C/G (N = 750), 2954 G/C (N = 845), and haplotypes defined by these SNPs were also studied.In CAP patients the genotype -174 GG were associated with protection against acute respiratory distress syndrome (ARDS) (p = 0.008, OR = 0.4, 95% CI 0.2-0.8). No other significant associations were observed. However, in patients with P-CAP multivariate analysis adjusted for age, gender, co-morbidity, hospital of origin, and severity (pneumonia severity index, PSI) showed that the IL6 -174 GG genotype was protective against the development of ARDS (p = 0.002, OR = 0.25, 95% CI 0.07-0.79), septic shock (p = 0.006, OR = 0.46, 95% CI 0.18-0.79), and multiple organ dysfunction syndrome (p = 0.02, OR = 0.53, 95% CI 0.27-0.89). P-CAP patients homozygous for IL6 -174 G also showed a higher survival in a logistic regression analysis adjusted for age, gender, co-morbidity, hospital of origin, and PSI (p = 0.048, OR = 0.27, 95% CI 0.07-0.98).Our results indicate that the IL-6 -174 GG genotype is associated with lower severity and mortality in patients with P-CAP. This effect was higher than that observed in patients with CAP irrespective of the causal pathogen involved. Our results highlight the importance of the causal pathogen in genetic epidemiological studies in sepsis.
ISSN: 0342-4642
DOI: 10.1007/s00134-011-2406-y
Source: Intensive Care Medicine [ISSN 0342-4642], v. 38, p. 256-262
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